Using economic and social data to improve veterinary vaccine development: Learning lessons from human vaccinology

The drivers of vaccine development are many and varied. They include, for example, recognition of the burden of a vaccine-targeted disease, prioritisation of the multiple problems associated with a disease, consideration of the differing socio-economic situations under which vaccines are used, the influence of advocacy groups, and assessment of the feasibility of large-scale vaccine manufacture and distribution. In the field of human health, data-driven development of vaccines is becoming increasingly common through the availability of reliable information on the Global Burden of Disease (GBD) and stringent evaluations of vaccination programmes utilising empirical data on costing and effectiveness, and standardised cost-effectiveness thresholds. The data generated from such analyses allow policymakers, implementing partners, industries and researchers to make decisions based on the best, and most contextually relevant, available evidence. In this paper, we wish to explore the current use of economic and social data for the development of veterinary vaccines. Through comparison with the development of human vaccines, we will look for opportunities in animal health sciences to better integrate socio-economic data and analyses into the process of veterinary vaccine selection, development, and field implementation. We believe that more robust animal health impact assessments could add value to veterinary vaccine development by improving resource allocation and animal disease management

Notas clínicas

Diagnostico diferencial de la angina de pecho / Determinación de los esteres de la colesterina por el procedimiento microquímico de Bang / Metabolismo de la colesterin

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues